The main objective of this proposal is to test the hypothesis that two types of nutritional manipulations (fasting and supplemented fasting) disrupt the homeostasis of the reproductive endocrine system of adult men and women by exerting an effect on one or more key points in the hypothalamic-pituitary axis (i.e., pituitary secretion, gonadotropin metabolism and gonadotropin excretion). Three main approaches will be utilized: 1) studies in human volunteers; 2) validation of a monkey model; 3) studies in the rat. In the human studies the objectives are: 1) to closely monitor the gonadotropin metabolic pathways during nutritional alterations in post-menopausal (PMW) cycling women and men. Gonadotropin secretion characteristics will be derived from both studies of endogenous pulsations and the response of the pituitary to exogenous LHRH administered by continuous infusion; 2) to determine whether the degradation and excretion properties of circulating gonadotropins are attributable to the presence of heterogeneous forms within the circulation (by comparing immunoreactive to bioactive potencies in in vitro bioassays during different nutritional states); 3) to examine the influences of steroid replacement in PMW upon gonadotropin excretion during fasting and refeeding; and 4) to establish the relative safety of the two weight reduction regimens upon the menstrual cycles of young women with immediately preceding ovulatory cycles. The objective of the primate studies is to validate the bonnet monkey (Macaca radiata) as a model for the gonadotropic metabolic alterations occurring as a result of nutritional alterations in the human. Since the effects of fasting on the hypothalamic, pituitary, gonadal axis can be studied directly in the rat, we are initiating studies to a) compare the rat model to that of the human and monkey, and b) to make direct measurements of peptides and steroids in the affected organs.